PREPARATION  OF  SOME  NEW  HYDROXY 
A(’n>S  BY  THE  ACTION  OF  CHLOR HYDRINS 
ON  SODIUM  M ADONIC  ESTER 

BY 

HERBERT  ORION  CALVERY 


TMESIS 


FOR  THE 

DEGREE  OF  BACHELOR  OF  ARTS 

I N 

CHEMISTRY 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 

UNIVERSITY  OF  ILLINOIS 


1921 


Afl 


Vb*\ 

C\2> 


UNIVERSITY  OF  ILLINOIS 


CNJ 

uu 


My_25,__I92l__ 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

__K2HBEHT  ORION  _CALVERY  _ 

ENTITLED ?.HEPAMTI  ON  _ QF_  J3  0ME_  J$W_  H YD  ROXY  _ AO  I _D_  S_  BY  _THE_  _AG1  I OIL  _ . 

OP _ JO H L OR H YD R_IN  S _ OH. _ SOB  I U M JAAL  0 II I _C  _ E S TER 

IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF ^_^_he_lor__o_f _ Ar ts__in _Chanis_t ry_ 


C* J.  

Instructor  in  Charge 

Approved  : 

HEAD  OF  DEPARTMENT  OF 

4A3508 


. 


-2- 


ACKNOY.T1EDGMENT . 

The  writer  wishes  to  express  his  appreciation  to  Dr.  Marvel 
for  his  constant  and  helpful  directions  and  suggestions  during 
these  preparations.  His  advice  and  helpfulness  has  been  greatly 
appreciated. 


Digitized  by  the  Internet  Archive 

in  2016 


https://archive.org/details/preparationofsomOOcalv 


-3- 


TABLE  OF  CONTENTS. 

I . Acknowledgment . 2 . 

II.  Introduction.  4. 

III.  Historical.  4. 

1.  Ethylene  chlorhydrin.  4. 

2.  Trimethylene  chlorhydrin.  5. 

3.  Trimethylene  iodhydrin.  8. 

4.  Trimethylene  chloracetate . 8. 

5.  Trimethylene  iodacetate.  9. 

6.  Phenoxy  propyl  bromide.  9. 

7.  Phenoxy  propyl  diethyl  malonate . 9. 

8.  Normal  nhenyl  octyl  ether.  10. 

9.  Normal  octyl  bromide.  10. 

10.  Normal  octyl  alcohol.  10. 


IV.  Theoretical. 

V . Experimental . 

1 . Prenaration  of 

2.  Prenaration  of 

3.  Prenaration  of 

4.  Prenaration  of 

5.  Preparation  of 

6.  Preparation  of 

7.  Preparation  of 

8.  Prenaration  of 

9.  Preparation  of 

10.  Prenaration  of 

11.  Prenaration  of 

VI.  Summary. 

VII.  Bibliography. 


11. 


p-hydroxy  ethyl  malonic  ester.  14. 

trimethylene  chlorhydrin.  14. 

trimethylene  iodhydrin.  16. 

trimethylene  chloracetate.  17. 

trimethylene  iodacetate.  17. 

phenoxy  propyl  bromide.  17. 

phenoxy  propyl  diethyl  malonate.  18. 

phenoxy  valeric  acid.  19. 

phenoxy  propyl  butyl  diethyl  malonate.  19. 
normal  phenyl  octyl  ether.  20. 

normal  octyl  bromide.  20. 

20. 

21. 


' 


, 


x 


. 


. 


. 


-4- 


Introduction. 

Within  recent  years  a great  amount  of  work  has  been  done  on 
the  preparation  of  chlorhydrins . The  result  of  this  work  has  been 
some  cheap  methods  of  their  preparation  and  making  them  easily  a- 
vailable.  Malonic  ester,  from  which  sodium  malonic  ester  is  pre- 
pared, is  also  quite  accessable . Since  theoretically  a condensa- 
tion of  these  two  classes  of  compounds  was  possible  it  was  thought 
that  some  new  hydroxy  acids  might  be  synthesized  which  would  be  of 
interest . 

The  expensive  and  inefficient  methods  by  which  these  acids 
have  been  made  have  made  their  use  quite  limited.  If  the  method  of 
preparation  which  the  writer  tried  and  will  discuss  in  this  paper 
had  been  successful  a new  series  of  compounds  of  the  form 

0=G 0 

CII*  -CHi-6-CHj.-CHa 

6 6=0 

would  have  been  prepared.  These  are  dilactones.  They  would  have 
been  made  by  the  following  reaction: 

H00C  0=9 0 

IIO-CH*  -CH2.-C-CHs.-CH2. -OH  — > CH*  -CH^-C-CIIi-iHa. 

C00H  6 C=0 

The  acids  which  were  possible  by  these  condensations  were  the 
p y^and  c9-hydroxy-dicarboxylic  and  also  mono -carboxylic  acid. 

HISTORICAL. 

1.  Ethylene  chlorhydrin. - Ethylene  chlorhydrin  was  first  pre- 
pared by  Wurtz1  in  1859.  He  saturated  some  ethylene  glycol  with 
hydrochloric  acid  gas . He  sealed  the  saturated  solution  in  tubes 
and  kept  it  at  a temperature  of  100  degrees  for  several  hours . On 
removing  the  product  from  the  tubes  he  found  a product  which  had  a 
constant  boiling  point  of  128  degrees.  This  on  analysis  proved  to 
be  ethylene  chlorhydrin. 


- 


I • 


v 


. 


-5- 


Carius2  prepared  ethylene  chlorhydrin  by  an  entirely  differ- 
ent method  in  1863.  His  method  of  preparation  was  to  treat  ethy- 
lene with  2-3  io  hypochlorous  acid.  He  fitted  a large  flask  with  a 
tightly  fitting  stopper  and  filled  it  with  ethylene  gas . He  then 
poured  on  the  gas  2-3  $ hypochlorous  acid.  The  hypochlorous  acid 
was  in  water  solution.  After  a short  time  he  distilled  the  result- 
ing product  and  obtained  a product  which  gave  all  tests  for  ethyl- 
ene chlorhydrin.  He  gave  its  boiling  point  as  130  degrees. 

Schorlemmer3  prepared  ethylene  chlorhydrin  by  saturating 
ethylene  glycol  with  hydrochloric  acid  gas  and  allowing  it  to 
stand  for  several  hours. 

Ladenburg^  modified  the  methods  which  had  previously  been 
used  and  placed  the  glycol  in  a distilling  bulb  and  passed  dry 
hydrochloric  acid  gas  through  it  at  a temperature  of  148  degrees. 
After  the  reaction  started  he  raised  the  temperature  to  about  160 
degrees  and  collected  the  distillate  which  contained  water,  chlor- 
hydrin, hydrochloric  acid  gas,  etc.  He  extracted  the  distillate 
with  ether  which  removed  the  ethylene  chlorhydrin  and  dried  it 
over  potassium  carbonate.  He  evaporated  off  the  ether  when  the 
product  was  dry  and  distilled  the  residue.  He  redistilled  it  a 
second  time  in  order  to  purify  it,  obtaining  a yield  of  60  $. 

Ethylene  chlorhydrin  has  a boiling  point  of  128  degrees 
(Wurtz).  At  8 degrees  its  specific  gravity  is  1.24.  It  is  mis- 
cible with  water  in  all  proportions.  Unon  reduction  and  hydrolysis 
it  gives  hydrochloric  acid  and  alcohol. 

2.  Trimethylene  chlorhydrin*-  Trimethylene  glycol  from  which 
trimethylene  chlorhydrin  is  made  was  first  prepared  in  1871  from 
trimethylene  bromide  by  Germont n< . The  bromide  treated  with  gla- 


. 

• ‘ . t . J. 

• •]  ■ ;:••••  ' ■.  «?:■  ■;  , • ; • . ! , r 


• ' / 


-G- 


cial  acetic  acid  and  silver  acetate  yielded  the  diacetate  which 
boiled  at  203  degrees.  This  compound  was  treated  with  barium  hy- 
droxide and  yielded  a compound  boiling  from  208-218  degrees.  Analy- 
sis and  reactions  proved  it  to  be  trimethylene  glycol. 

Reboul^  also  prepared  it  in  1874  by  the  same  method  giving 
the  boiling  point  as  216  degrees. 

By  accident  Freund"^,  while  trying  to  prepare  normal  butyl 
alcohol  by  fermentation  of  glycerol,  found  that  some  other  com- 
pound was  being  formed  in  considerable  quantity.  This  compound 
when  distilled  with  steam  and  then  redistilled  proved  to  be  pure 
trimethylene  glycol. 

The  most  important  method  is  that  discovered  by  A.  A.  Noyes 
and  W.  H.  Watkins7  in  1895.  A soart  concern  near  Boston  was  having 
trouble  getting  glycerol  of  the  proper  specific  gravity.  The  cause 
was  attributed  to  some  impurity.  They  sent  some  of  the  light  mater 
ial  to  Noyes  and  Watkins  who  subjected  it  to  fractional  distillation 
They  found  that  it  contained  38  $ trimethylene  glycol. 

Another  method  is  that  of  Niederist^.  His  method  was  to  treat 
trimethylene  bromide  with  moist  silver  oxide.  The  method  that  is 
most  extensively  used,  in  fact  it  is  almost  entirely  used,  is  the 
fermentation  method.  It  is  the  most  inexpensive  and  the  best 
yields  are  obtained  by  it. 

The  only  use  of  trimethylene  glycol  in  this  problem  is  its  use 
as  the  main  product  in  the  preparation  of  trimethylene  chlorhydrin. 

Trimethvlene  chlorhydrin  was  prepared  first  by  Reboul9  in 
1774  by  heating  trimethylene  glycol  saturated  with  hydrochloric 
acid  gas  in  sealed  glass  tubes  at  a temperature  of  100  degrees  for 
several  hours . When  the  mixture  was  removed  from  the  tubes  and 


* 

« • 

- 

' 

' 

• >'  . •>  . /t  rtvl  ' 


. • . ! ■ 

1 • 

■ • r ; r • 


submitted  to  fractional  distillation  it  was  found  that  both  tri- 
methylene  chloride  and  trimethylene  chlorhydrin  were  formed.  They 
were  separated  by  fractional  distillation. 

The  chlorhydrin  method  of  Reboull°>  as  it  is  called,  is  the 
method  that  has  been  used  previously.  It  consists  in  passing  dry 
hydrochloric  acid  gas  through  trimethylene  glycol  in  the  cold.  His 
method  was  to  pass  the  gas  through  for  16  hours  and  then  fraction- 
ally distill  the  resulting  product.  By  this  method  50  $ yields 
were  claimed  but  the  writer  followed  it  out  carefully  and  was  never 
able  to  obtain  more  than  a 40  ^ yield. 

This  method  of  preparation  was  used  by  Derrick  and  Bissell11 
but  was  modified  slightly,  in  the  time  especially  in  which  they 
allowed  the  gas  to  pass  through  the  glycol.  Into  130  grains  of  the 
glycol  they  passed  hydrochloric  acid  gas  for  three  hours  and  then 
fractionally  distilled  the  product.  They  obtained  a 25  gram  yield. 

Trimethylene  chlorhydrin  boils  at  160  degrees  and  has  a spec- 
ific gravity  of  1.123  at  17  degrees  and  is  only  slightly  soluble  in 
water • 

The  best  method  for  the  preparation  of  trimethylene  chlor- 
hydrin is  a method  which  is  similar  to  the  method  used  by  Reboul^0 
for  the  preparation  of  ethylene  chlorhydrin.  It  is  the  method  used 
here  in  the  University  of  Illinois  laboratories  and  has  been  im- 
proved by  the  writer.  It  will  be  described  in  full  in  the  theor- 
etical and  experimental  part  of  this  paper.  It  eliminates  the  seal- 
ed tube  method  which  is  a great  advantage  over  most  of  the  other 
methods  used. 

The  corresponding  bromhydrin  has  also  been  prepared  by 
Fruhlingl^  in  1882.  A mixture  of  100  parts  of  trimethylene  glycol 
and  100  parts  of  hydrobromic  acid  (48$)  was  saturated  with  hydro- 


' 


-- 


* 


- fc 


. 


-8- 


broraic  acid  gas  and  heated  from  4-5  hours  on  a water  bath.  Both 
trimethylene  bromide  and  trimethylene  bromhydrin  were  formed.  The 
bromhydrin  is  slightly  soluble  in  water  while  the  bromide  is  not 
and  a complete  separation  may  be  effected  by  repeated  washing  with 
water.  The  wash  water  was  neutralized  with  sodium  hydroxide  and 
shaken  with  ether.  The  ether  was  distilled  off  on  the  water  bath 
and  the  residue  distilled  at  a higher  temperature  under  diminished 
temperature.  The  product  distilled  at  from  98-112  degrees  under 
a pressure  of  about  180  mm. .and  has  a specific  gravity  of  1.5304 
at  20  degrees.  It  is  soluble  in  six  parts  of  cold  water. 

3.  Trimethylene  iodhydrin.  Trimethylene  iodhydrin  was  pre- 
pared by  Henry*3  in  1879  from  the  chlorhydrin.  A solution  of  the 
chlorhydrin  in  methyl  alcohol  was  treated  with  sodium  iodide  and 
the  mixture  allowed  to  stand.  Afterwards  the  product  was  distilled 
and  the  iodhydrin  was  found  to  boil  at  225  degrees  without  decom- 
position and  had  a specific  gravity  of  2.349  at  13  degrees.  It 
had  a sweet  smell  and  a sharp  taste.  It  is  soluble  in  water  al- 
cohol and  ether.  The  writer  has  prepared  the  iodhydrin  by  the 
same  method  except  that  acetone  was  used  as  a solvent  instead  of 
methyl  alcohol  because  of  the  fact  that  sodium  chloride  is  insol- 
uble in  acetone  while  the  sodium  iodide  is  very  soluble. 

4.  Trimethylene  chloracetate . Derrick  and  Bissell14  prepared 
this  compound  to  use  in  the  preparation  of  trimethylene  oxide. 

Their  method  was  to  take  300  grams  of  the  chlorhydrin  in  a flask 
and  allow  250  grams  of  acetyl  chloride  to  drip  slowly  on  the  chlor- 
hydrin. The  flask  was  then  fitted  with  a condenser  for  downward 
distillation  and  the  mixture  distilled.  375  grams  of  trimethylene 
chloracetate  were  obtained.  It  is  a clear  colorless  liquid  with  a 


sharp  odor  and  a boiling  point  of  164  degrees . 


♦ a-tn 


- 


. 


- . < •- 


-9- 


5.  Trimethylene  iodacetate.  Trimethylene  iodacetate  was  pre- 
pared hy  Henry*5  in  the  same  manner  as  the  iodhydrin.  He  dissolved 
the  corresponding  chlor  compound  in  methyl  alcohol  and  added  sod- 
ium iodide.  The  iodine  replaces  the  chlorine  just  as  in  the  other 
cases . 

The  iodacetate  is  also  prepared  hy  the  same  method  used  in  the 
preparation  of  the  corresponding  chloro  compound.  It  was  used  hy 
Ladenburg15  in  1883.  It  has  a boiling  point  of  207-210  degrees. 

6.  Phenoxy-propyl-bromide . Phenoxy-propyl-hromide  was  pre- 
pared hy  Lohmann*7  in  1891.  His  method  was  to  take  one  mole  of 
phenol,  one  mole  of  trimethylene  bromide,  and  about  two  moles  of 
sodium  ethylate  and  reflux  on  a steam  hath  for  a few  hours.  After 
distilling  off  the  alcohol  he  distilled  the  residue  under  reduced 
pressure  and  obtained  the  desired  product  in  good  yields. 

The  same  method  has  been  used  here  at  the  University  of  Ill- 
inois and  better  results  have  been  obtained  by  varying  conditions. 

The  method  of  Wohl  and  Berthold18  for  preparing  phenoxy-ethyl- 
bromide  was  used  by  the  writer  and  excellent  results  were  obtained. 
This  method  is  to  take  a large  flask  fitted  with  a reflux  condenser 
and  place  in  it  100  grams  of  phenol,  125  grams  of  trimethylene 
bromide,  and  1000  grams  of  water.  Then  dissolve  a slight  excess 
of  sodium  hydroxide  in  250  cc . of  water  and  add  this  to  the  solution 
in  50  cc.  portions  every  half  hour  and  then  reflux  the  mixture  two 
hours  longer  before  removing  the  flame.  There  are  two  layers  and 
the  heavy  one  contains  the  compound  desired.  Separate  the  two 
layers  in  a separatory  funnel  and  distill  under  reduced  pressure. 

The  excess  trimethylene  bromide  can  all  be  recovered. 

7.  Phenoxy-propyl-diethyl-malonate . This  compound  has  only 


L 


. r\ 

‘ 

' 

• ' 't  ■ 

...  . - t ■ 

* 

■ 

• ; ' 


-10- 


1 Q 

"been  prepared  by  Gabriel  . He  took  34  grams  of  raalonic  ester,  34 
grams  phenoxy-propyl-chloride , 8 grams  of  sodium  and  dissolved  the 

whole  mixture  in  absolute  alcohol  dissolving  the  sodium  first.  He 
refluxed  this  mixture  on  the  water  bath  for  a few  hours  and  then 
distilled  off  the  alcohol,  added  water  to  dissolve  the  sodium 
chloride  in  which  his  product  was  an  insoluble  oil.  He  separated 
the  two  by  means  of  a separatory  funnel  and  obtained  a yield  of  45 
grams  of  the  crude  ester  without  distillation.  Gabriel  then  sapon- 
ified the  crude  ester  and  obtained  upon  neutralization  the  dicar- 
boxylic  acid.  He  obtained  a 20  gram  yield  of  the  dicarboxylic  acid 
He  then  heated  this  acid  and  by  driving  off  carbon  dioxide  he  ob- 
tained the  mono-carboxylic  acid.  It  crystallizes  from  ligroie  in 
nice  white  crystals  which  have  a melting  point  of  64  degrees.  From 
this  compound  he  obtained  the  delta  hydroxy  acid  by  splitting  off 
the  phenyl  group  with  hydrochloric  acid  in  sealed  tubes  and  then 
treating  the  chlor  compound  with  silver  oxide  and  water. 

8.  Normal-phenyl-octyl -ether . Perkins20  prepared  normal- 
phenyl-octyl-ether  in  1896  by  the  following  method.  He  took  one 
mole  of  octyl  iodide,  which  had  been  prepared  from  octyl  alcohol, 
with  three  moles  of  phenol  and  one  mole  of  sodium  hydroxide  with  a 
little  water  and  placed  the  substances  in  a Wurtz  flask  and  heated 
until  he  thought  the  reaction  complete.  He  then  removed  the  con- 
tents and  distilled.  He  obtained  normal-phenyl-octyl-ether.  It  is 
a solid  at  8 degrees  and  boils  at  285  degrees  under  atmospheric 
pressure . 

9.  Normal  octyl  bromide.  Theodore  Zincke21  prepared  octyl 
bromide  by  treating  octyl  alcohol  with  hydrobromic  acid  gas.  The 
gas  is  passed  through  the  alcohol  and  the  reaction  takes  place. 


. ' 

1 

1 'a 


■ • 


, ■ ■ 


-11- 


The  bromide  has  a boiling  point  of  198  degrees. 

10.  Normal  octyl  alcohol.  The  first  and  only  method  of  ob- 
taining octyl  alcohol  was  from  nature.  Branchimont  and  Zincke22 
found  it  in  combination  with  acetic  acid  and  butyl  alcohol  in  the 
plant  Heracleum  Spondylium  and  separated  them  by  fractional  dis- 
tillation. It  has  a boiling  point  of  195.5  degrees. 

THEORETICAL. 

The  first  compound  to  be  prepared  in  the  synthesis  of  hydroxy 
acids  is  the  condensation  product  of  one  of  the  chlorhydrins , for 
example  ethylene  chlorhydrin,  with  sodium  raalonic  ester.  The  sod- 
ium malonic  ester  is  prepared  by  the  treatment  of  malonic  ester 
with  sodium  dissolved  in  absolute  alcohol.  The  condensation  should 
take  place  according  to  the  following  reaction 

COOC^H*  COOCxHiT 

HO-CHa-CHx-Cl-f  Na-C-II  > HO-CH^-CH^-C-H  + NaCl 

COOCaH*  C00CaH^ 

It  was  observed  that  the  theoretical  amount  of  sodium  chloride  was 
obtained  but  when  the  condensation  product  was  distilled  under  re- 
duced pressure  that  only  about  15  $ of  the  theoretical  yield  of 
the  hydroxy  ester  was  obtained.  This  yield  is  about  the  same  as 
that  Fittig  and  Roder2^  when  they  made  the  same  product  by  treating 
sodium  malonic  ester  with  ethylene  oxide. 

The  general  method  for  running  malonic  ester  syntheses  is  to 
reflux  the  mixture  until  neutral.  In  making  these  runs  however  the 
time  was  varied  with  apparently  no  change  whatever  in  the  results. 

A list  of  the  substances  used  in  these  attempted  preparations 
is  as  follows:-  ethylene  chlorhydrin,  trimethylene  chlorhydrin, 
chlor  ethyl  acetate,  ethylene  bromide,  trimethylene  bromide,  tri- 
methylene iodhydrin,  trimethylene  chloracetate , trimethylene  iod- 


- • I 

> '•  •'  ' 


-12- 


acetate,  and  phenoxy  propyl  bromide.  Of  these  only  the  first  and 
last  gave  any  yields  at  all,  the  first  giving  a yield  of  never 
more  than  15  and  the  last  giving  as  high  as  a 63  ^ yield.  It 
was  quite  interesting  to  note  however  what  happened  when  trimethyl- 
ene chloracetate  and  trimethylene  iodacetate  were  used.  In  the 
process  of  distillation  under  reduced  pressure  every  time,  when 
the  temperature  had  reached  about  140  degrees  under  20  mm.,  the 
contents  of  the  flask  became  a deep  red  gel  which  would  expand  and 
fill  the  flask  and  not  distill  at  all.  It  was  not  identified. 

Since  the  phenoxy  propyl  bromide  would  react  giving  good 
yields  the  work  of  Gabriel  was  repeated  as  far  as  the  following  re- 
actions indicate. 

COOC*  H s 0000*115 

(1)  O'OCHj.-CIU-CHi-Br  Na-C-H  >0OCHZ-CHZ -CIV-C-H  + NaBr 

0000*11$-  C00C*IV 

0000*115*  COOH 

(2)  0"QCH*  -CH^-CH^-C-H  0OCIIZ-CHZ-CH  -C-H 

COO  C*  Hi"  COOH 


(3) 


COOH 

0OCHZ  -CH^  -CHZ  -C-H 
6 oo  h 


heat 


0 OCH*  -cii^-ch^-c^-cooh 

M.P.  64  degrees. 


Because  it  was  desired  to  observe  some  more  reactions  with  the  same 
compound  the  writer  did  not  follow  Gabriel’s  work  any  farther  but 
attempted  the  preparation  of  normal  oc£yl  alcohol  by  the  following 
series  of  reactions. 

COOCJV 

(1)  0OCHZ-CHZ -CH, -Br  Na-C-CH* -CH*-CHZ-CH, > 

COOC*  Hr 

COOC  H 

^0CHz-CH* -CH* -C-CH^-CH* -CH, -OH  3 -f  NaBr 
COOC  H 

This  compound  upon  saponification  gives  the  dicarboxylic  acid  and 
we  have, 


V 


• t: 


- 


-13- 


COOH 


fuse 


(2)  OOCH^-CH.-CH.-C-CH.-CH^CH.-CH^  soda_llme 


QOCH^ ( CH^ )t  CH , 


(3)  QOCH  (CH  ) CH  HBr  (48$)— > Br-CIL^CI^  )6 CH^  ~h  CJI^OH 


(4)  Br-CH^  -CI^-CH  ,-CH^-CH*  -CHi-CIIx-CH3  -A& 9.  ,_j> 

Hj  0( 


IIO -CH^  -CH 2 -CH * -CH^  -CH  ^ -CII ^ -CH  a -CH  3 

For  lack  of  time  the  last  step  was  not  run  at  all  and  the  pre- 
paration of  the  bromide  was  tried  only  once . The  first  reaction 
was  carried  out  just  exactly  the  same  as  with  malonic  ester  using 
butyl  malonic  ester  instead.  A yield  of  63  $ of  the  calculated 
amount  was  obtained. 

In  the  fusion  with  soda-lime  to  drive  off  carbon  dioxide  it 
was  interesting  to  note  that  the  phenyl  group  was  removed  also  and 
some  ocfcyl  alcohol  was  obtained  at  this  point. 

EXPERIMENTAL. 

1.  ^-hydroxy  ethyl  diethyl  malonate.  The  method  used  in  the 
preparation  of  this  compound  is  the  general  method  given  by  W.  A. 
Noyes  for  carrying  out  a synthesis  with  malonic  ester. 

To  ion  cc.  of  absolute  alcohol  in  a round  bottom  flask  fitted 
with  a reflux  condenser  add  5.8  grams  of  metallic  sodium  and  allow 
the  mixture  to  cool,  then  add  40  grams  of  malonic  ester  and  shake 
well.  After  shaking  add  through  the  condenser  20  grams  of  dry 
ethylene  chlorhydrin,  place  on  a steam  bath  and  reflux  until  neu- 
tral. The  time  required  for  this  is  about  three  hours.  Now 
change  the  condenser  and  arrange  for  downward  distillation.  Dis- 
till off  the  alcohol.  This  requires  about  three  hours.  Pour  into 
the  flask  enough  water  to  dissolve  the  sodium  chloride  and  separate 
the  two  resulting  layers  in  a separatory  funnel.  The  brown  oily 
layer  contains  the  product  desired.  Disregard  the  water  portion. 


- 

. 


, 


-14- 


Distill  the  oil  under  reduced  pressure.  There  are  two  main  frac- 
tions one  of  which  is  malonic  ester  which  distills  from  120-130  de- 
grees under  25  mm.  of  pressure,  the  other  is  the  ester  which  dis- 
tills from  170-180  degrees  under  this  pressure.  The  yields  vary 
but  the  best  obtained  was  15  $ of  the  calculated  amount . Refluxing 
for  a longer  time  did  not  change  the  yield.  Neither  an  excess  of 
malonic  ester  nor  of  ethylene  chlorhydrin  changes  the  per  cent 
yield.  The  condensation  with  trimethylene  chlorhydrin,  trimethy- 
lene iodhydrin,  trimethylene  iodacetate,  trimethylene  chloracet- 
ate,  chlorethyl  acetate,  trimethylene  bromide  and  ethylene  bromide 
all  gave  practically  negative  results.  There  was  always  a malonic 
ester  fraction  and  a varied  amount  of  tar. 

2.  Trimethylene  chlorhydrin.  A hydrochloric  acid  generator 
is  made  in  the  following  manner.  A five  liter  round  bottom  flask 
is  fitted  with  a two  hole  rubber  stopper  through  which  are  inserted 
a dropping  funnel  and  an  outlet  tube.  In  the  dropping  funnel  is 
placed  commercial  sulfuric  acid.  In  the  flask  are  placed  4 pounds 
of  salt  and  about  two  liters  of  37  $ hydrochloric  acid. 

A 100  cc.  wide  mouth  round  bottom  flask  is  fitted  with  a four 
hole  rubber  stopper  through  which  are  inserted  a dropping  funnel, 
a thermometer  reaching  nearly  to  the  bottom  of  the  flask,  one 
glass  tube  reaching  to  the  bottom  of  the  flask,  and  another  glass 
tube  extending  just  through  the  stopper  is  connected  to  a water 
condenser.  This  small  flask  is  clamped  to  a ring  stand  and  25  cc. 
(never  more  than  40  cc.)  of  trimethylene  glycol  are  run  into  it. 
About  one  third  of  the  bulb  is  immersed  in  an  oil  bath  and  the  bath 
heated  until  the  thermometer  reading  is  160-180  degrees . 

The  tube  extending  to  the  bottom  of  the  small  flask  is  con- 
nected to  the  hydrochloric  acid  generator  and  a very  rapid  stream 


. 


-15- 


of  hydrochloric  acid  gas  is  passed  through  the  glycol.  Trimethy- 
lene chlorhydrin,  water,  hydrochloric  acid,  and  some  side  re- 
action products  begin  to  distill  over  and  are  collected;  excess 
hydrochloric  acid  gas  being  absorbed  by  the  water.  As  rapidly  as 
the  glycol  is  used  it  is  replenished  from  the  dropping  funnel,  al- 
ways keeping  the  amount  in  the  flask  constant.  The  process  is  con- 
tinuous and  as  much  material  may  be  run  through  as  is  desired  with- 
out changing  the  apparatus,  except  to  replenish  the  hydrochloric 
acid  and  salt  in  the  generator. 

It  has  been  found  as  the  following  table  shows  that  one  kilo 
of  glycol  may  be  run  through  this  apparatus  in  four  hours,  at 
which  rate  best  results  are  obtained. 

Place  the  distillate  on  a steam  bath  and  allow  all  the  hydro- 
chloric aeid  gas  to  be  distilled  off  that  can  be.  About  one  hour 
is  required  for  this.  Afterward  place  it  in  a flask  with  a frac- 
tionating column  and  carefully  distill,  using  pieces  of  clay  to 
prevent  bumping.  The  fraction  distilling  up  to  158  degrees  is 
collected  in  a separate  container.  The  part  distilling  from  158- 
164  degrees  is  good  chlorhydrin  and  is  not  treated  any  further. 

The  re  xt  fraction  boiling  from  164-180  degrees  is  collected  and  re- 
distilled once,  collecting  the  fraction  from  158-164  degrees  as 
above.  The  fraction  distilling  above  164  degrees  is  combined  with 
the  original  high  boiling  fraction,  and  the  whole  is  distilled 
collecting  what  comes  over  below  220  degrees.  This  is  mainly  tri- 
methylene glycol  with  some  chlorhydrin  in  it.  This  fraction  may 
be  run  again  and  good  yields  obtained  from  it.  Above  220  degrees 
there  is  a high  boiling  bar  which  will  not  distill  (possibly  high 
boiling  ethers).  The  first  fraction  contains  water  and  about  50 

trimethylene  chlorhydrin.  This  distillate  is  neutralized  with 


’ 

fc  , 


- 


-16- 


commercial  sodium  carbonate  and  the  chlorhydrin  separates  out.  It 
is  then  poured  off  and  distilled,  a small  amount  of  low  foiling 
product  "being  obtained. 


By  running  the  fraction  from  164-220  degrees  a second  time  and 
treating  the  distillate  as  described  above  a 70  $ yield  was  obtain- 
ed. 


Glycol 

grams 

H SO 
lbs . 

Salt 

lbs. 

HC1 

lbs 

Chlor- 
hydrin 
grams . 

Recov. 

Glycol 

grams 

Low- 
boiling 
f rat . 

Tar 

grams 

~ ■ 
Time 
hrs . 

Times 

fract- 

ionated. 

190 

4 

5 

2 

120 

11 

80 

31 

2 

5 

440 

291 

25 

50 

50 

5 

3 

220 

148 

15 

30 

45 

3 

3 

200 

138 

24 

20 

50 

2 

3 

210 

4 

5 

2 

158 

10 

50 

2 

2 

1000 

12 

10 

6 

876 

110 

55 

210 

7 

2 

500 

7 

5 

5 

487 

30 

95 

2 

2 

500 

8 

5 

5 

378 

105 

10 

85 

2 ' 

2 

The  above  table  shows  a record  of  the  runs  made.  The  seventh  and 
eighth  runs  were  the  best  giving  the  highest  yields.  This  is  due 
to  the  fact  that  a very  rapid  stream  of  hydrochloric  acid  gas  is 
passed  through  the  glycol  at  a temperature  of  160-180  degrees. 

3.  Trimethylene  iodhydrin.  This  is  prepared  by  the  method  of 
Henry  with  the  modification  that  acetone  is  used  for  a solvent  in- 
stead of  methyl  alcohol. 

Put  400  cc.  of  acetone  in  a liter  round  bottom  flask.  Dis- 
solved one  mole  of  sodium  iodide  in  the  acetone.  To  this  solution 


. 


-17- 


is  added  one  mole  of  trimethylene  chlorhydrin  and  the  whole  is  al- 
lowed to  stand  over  night.  Sodium  chloride  is  filtered  off,  the 
acetone  distilled  off  and  the  final  product  distilled  under  reduc- 
ed pressure.  A slightly  brown  product  was  obtained.  The  yield  was 
45  of  the  theoretical  amount. 

4.  Trimethylene  chloracetate . In  a round  bottom  flask  is 
placed  one  mole  of  trimethylene  chlorhydrin  and  to  it  is  added  in 
course  of  half  an  hour  one  mole  of  acetic  anhydride.  Add  in  small 
portions  and  shake  well.  After  all  the  acetic  anhydride  has  been 
added  fit  the  flask  with  a condenser  for  downward  distillation  and 
distill.  The  chloracetate  comes  over  at  164  degrees  in  good  yields 
As  high  as  95  $ of  the  calculated  amount  is  obtained  by  this  pro- 
ceedure . 

5.  Trimethylene  iodacetate.  100  grams  of  trimethylene  chlor- 
acetate are  added  to  a solution  of  sodium  iodide  in  acetone  and  the 
mixture  allowed  to  stand  over  night.  The  sodium  chloride  is  then 
filtered  off  and  the  acetone  distilled  off  on  the  steam  bath.  The 
residue  is  distilled  under  reduced  pressure.  A product  is  obtained 
which  boils  at  208-211  degrees  under  atmospheric  pressure.  This  is 
trimethylene  iodacetate.  The  yield  is  53  ^ of  the  theoretical 
amount . 

6.  Phenoxy  propyl  bromide.  The  method  of  V/ald  and  Berthold 
is  used  in  the  preparation  of  phenoxy  propyl  bromide.  It  is  the 
same  method  used  for  the  preparation  of  phenoxy  ethyl  bromide.  A 
five  liter  flask  is  fitted  with  an  upright  condenser  and  a dropp- 
ing funnel.  In  the  flask  is  placed  1500  cc . of  water  700  grams  of 
trimethylene  bromide  and  310  grams  of  phenol  120  grams  of  solid 
sodium  hydroxide  is  dissolved  in  500  cc  of  water  and  this  placed  in 
the  dropping  funnel.  The  contents  of  the  flask  are  raised  to  boil- 


- 

I. 

* 

. 


-18- 


ing  and  at  about  40  minute  intervals  25-50  cc . of*  the  sodium  hy- 
droxide solution  is  admitted  to  the  flask.  After  all  the  sodium 
hydroxide  solution  is  added  the  contents  are  refluxed  for  two  hours 
longer.  There  are  two  layers  in  the  flask  and  when  this  is  allowed 
to  cool  they  are  separated  in  a separatory  funnel  and  the  heavy 
layer  which  contains  the  phenoxy  propyl  bromide  is  distilled  under 
reduced  pressure.  The  water  layer  containing  the  sodium  bromide  is 
neglected.  The  distillation  is  repeated  once  and  the  phenoxy  pro- 
pyl bromide  comes  over  at  180  degrees  under  25  mm.  of  pressure. 

250  grams  of  trimethylene  bromide  may  be  recovered  in  some  cases. 
Calculating  on  the  trimethylene  bromide  which  enters  into  the  re- 
action 87  <fo  of  the  theoretical  yield  may  be  obtained. 

7.  Phenoxy  propyl  diethyl  malonate.  In  this  preparation  the 
method  of  Gabriel  was  followed  at  first  without  knowledge  of  his 
having  performed  the  experiment.  Almost  identically  the  same  re- 
sults were  obtained  by  the  writer  as  he  obtained. 

Some  sodium  malonic  ester  is  prepared  from  alcohol  which  has 
been  distilled  over  sodium,  freshly  distilled  malonic  ester  and 
metallic  sodium.  To  a slight  excess  of  this  is  added  100  grams  of 
pure  phenoxy  propyl  bromide  in  a round  bottom  flask.  The  flask  is 
then  fitted  with  an  upright  condenser  and  placed  on  a steam  bath. 
Every  precaution  should  be  taken  to  prevent  any  moisture  getting 
into  the  flask.  The  mixture  is  allowed  to  reflux  over  night.  The 
condenser  is  then  arranged  for  downward  distillation  and  the  alcoh- 
ol distilled  off.  To  the  residue  is  added  enough  water  to  dissolve 
the  sodium  bromide.  The  oil  does  not  dissolve  in  water  to  any 
appreciable  amount.  The  oil  is  then  dried  or  distilled  immediate-  * 
ly  without  drying  under  reduced  pressure.  Under  20  mm.  of  pres- 
sure a clear  colorless  product  comes  over  at  220  degrees.  Analy- 


•f 

* 

■ 


' • 

! 

■ 

!.  1 

• 

... 

■ * 

* 

. 

. 

■ ' 

. ’ ■ ■ ; • 

. , 


-19- 


sis  and  saponification  equivalent  proves  this  to  he  phenoxy  propyl 
diethyl  malonate. 

Theory.  Found. 

C 65.3  $ 64.6  f0 

H 7.48  % 7.39  <f0 

8.  3-phenoxy  valeric  acid.  50  grams  of  phenoxy  propyl  diethyl 
malonate  are  put  into  a liter  round  bottom  flask  and  100  cc.  of  95 
per  cent  alcohol  is  added.  To  the  alcohol  solution  is  then  added 
an  excess  of  the  calculated  amount  of  alkali  required  to  saponify 
the  ester.  The  writer  used  alcoholic  sodium  hydroxide  in  all  these 
saponifications . This  is  refluxed  for  several  hours  and  the  con- 
tents of  the  flask  acidified  strongly  with  hydrochloric  acid.  200 
cc.  of  water  are  then  added  and  the  alcohol  is  distilled  off  on 
the  steam  bath.  The  acid  solution  is  extracted  with  ether  and  the 
ether  solution  dried  over  calcium  chloride.  The  ether  is  evaporatec 
and  the  phenoxy  propyl  malonic  acid  is  heated  in  an  oil  bath  at 
150  degrees  for  one  hour.  Carbon  dioxide  is  split  out  and  phen- 
oxy valeric  acid  is  obtained.  It  is  crystallized  from  ligroin  and 
has  a melting  point  of  64  degrees.  The  yield  is  60  of  the  cal- 
culated amount. 

9 Phenoxy  propyl  butyl  diethyl  malonate.  This  is  prepared 
almost  identically  like  the  phenoxy  propyl  diethyl  malonate.  To 
200  grams  of  absolute  alcohol  in  a two  liter  round  bottom  flask  are 
added  10  grams  of  sodium.  When  the  contents  of  the  flask  have 
cooled  125  grams  of  pure  butyl  malonic  ester  are  added  and  the  mix- 
ture shaken.  Then  100  grams  of  pure  phenoxy  propyl  bromide  are 
added.  The  flask  is  fitted  with  an  upright  condenser  and  placed  on 
a steam  bath.  The  mixture  is  refluxed  for  eight  hours.  After  re- 
moving from  the  steam  bath  200  cc . of  water  are  added  and  the  al- 
cohol distilled  off.  The  residue  separates  into  two  layers.  The 


. ... 


. 

. 

\1  . ■'  . 


. 


. 


. 

. ' 


- 


-20- 


water  layer  which  contains  only  sodium  bromide  and  water  is  disre- 
garded. The  oily  layer  is  distilled  under  reduced  pressure.  The 
phenoxy  ester  comes  over  at  225-230  degrees  under  a pressure  of  15 
ram.  The  theoretical  molecular  weight  is  350.  The  molecular  weight 
obtained  experimentally  by  saponification  is  352. 

Saponification  data: 

No.  of  grams  of  ester  saponified  5.7148 

No.  of  cc.  of  normal  alkali  used  33.03 

The  yield  is  63  $ of  the  theoretical  if  absolute  alcohol  and  fresh- 
ly distilled  butyl  malonic  ester  are  used. 

10.  Normal  octyl  phenyl  ether.  To  50  grams  of  phenoxy  pro- 
pyl butyl  diethyl  malonate  in  a liter  round  bottom  flask  is  added  ai: 
excess  of  alcoholic  sodium  hydroxide  and  the  contents  refluxed  for 
four  hours.  100  cc . of  water  are  then  added  and  the  contents  made 
distinctly  acid  with  hydrochloric  acid.  This  solution  is  extracted 
with  ether  and  the  ether  solution  dried.  The  ether  solution  is 
evaporated  on  a water  bath  to  remove  the  ether.  The  residue  is  ther 
taken  up  in  hot  ligroin  and  the  dicarboxylic  acid  is  allowed  to  cry- 
stallize out.  It  has  a melting  point  of  92  degrees.  This  dicar- 
boxylic acid  is  fused  with  soda-lime  in  order  to  remove  the  carbon 
dioxide  and  give  normal  oetyl  phenyl  ether,  flnly  15  grams  of  the 
ether  has  been  obtained  by  this  method.  It  has  a boiling  point  of 
182  degrees. 

11.  An  attempt  to  prepare  normal  octyl  bromide.  A 500  cc . 
round  bottom  flask  was  fitted  with  an  upright  condenser.  In  the 
flask  was  put  10  grams  of  normal  phenyl  octyl  ether  and  50  grams  of 
hydrobromic  acid  (48^)  and  the  contents  refluxed  for  eight  hours. 

In  the  top  of  the  condenser  was  fitted  a rubber  stopper  equipped 
with  a piece  of  glass  tubing  and  some  rubber  tubing  to  lead  away  the 


* ’ ' 1 ",  it  j}  • : 

. 


' 

t 

. 

’ ' 

. 

' 

i 

' ■ 


. 


-21- 


hydrobromic  acid  gas  which  escapes.  After  refluxing  eight  hours  the 
oily  layer  was  separated  and  distilled  under  atmospheric  pressure. 


Apparently  only  a slight,  if  any,  reaction  took  place  for  there 
was  still  the  strong  odor  of  the  phenyl  octyl  ether  and  the  boiling 
point  indicated  that  there  was  no  bromide  present.  The  ether  boils 
at  182  degrees  while  the  bromide  boils  at  195  degrees. 

SUMMARY . 

This  work  has  proved  that  the  chlorhydrins  and  the  chloracetates 
will  not  condense  with  sodium  malonic  ester.  Or  rather  what  is  more 
likely  that  they  do  condense  and  decompose  on  heating. 

Phenoxy  nropyl  bromide  will  condense  with  sodium  malonic  ester 
giving  good  yields.  It  will  also  condense  with  the  aliphatic  hydro- 
carbon condensation  products  of  sodium  malonic  ester  and  shows  a new 
possibility  for  the  preparation  of  phenyl  aliphatic  ethers,  the  al- 
iphatic halogen  compounds,  and  the  higher  aliphatic  alcohols. 


. 


' 


-22- 


BIBLIOGRAPHY. 

1. 

Wurtz 

Ann.  Ch.  Pharm. 

110 

; 125 

2. 

Carius 

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126 

; 197 

3. 

Schorlenmier 

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39; 

143. 

4. 

Lodenburg 

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16; 

1408 . 

5. 

Gerraont 

Ann.  Ch.  Pharm. 

158 

; 369-71. 

6. 

Reboul 

C R 

78; 

1773-76. 

7. 

Noyes  and  Watkins 

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17; 

890. 

8. 

Niederist 

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3; 

838-849. 

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Reboul 

C R 

76; 

270-72. 

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Fruhling 

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3; 

697. 

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Henry 

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Roy.  Belg. 

(3) 

32;  253. 

14. 

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38; 

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Henry 

Forts,  von  Bull.  Acad. 

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(3) 

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Lodenburg 

Ber. 

16; 

1407. 

17. 

Lohmann 

Ber . 

24; 

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26; 

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25; 

418. 

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